Circadian Rhythm of Blood Pressure and Heart Rate in Healthy Persons and Kidney Transplant Patients: Correlations with Activity

Fourteen diurnally active (07: 00–22: 39 h) normotensive healthy control subjects and 14 kidney transplant patients were studied by ambulatory blood pressure monitoring and wrist actigraphy simultaneously during one 24-h period. In the control group, circadian rhythms in systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure, heart rate (HR), and wrist activity were documented by cosinor analysis with comparable afternoon peak times. In contrast, circadian rhythms with afternoon acrophases were detected only in HR and wrist activity in the patient group. The correlation of wrist activity with HR in controls and patients was comparable. Wrist activity and blood pressure were associated (r = 0.65 DBP and 0.54 SBP; p < 0.05) in controls, while in patients the relationship was weak or absent (r ranging from 0.02 SBP to 0.22 DBP). In 6 of 14 patients, BP and wrist activity were negatively correlated, reflecting the existence of nocturnal hypertension. In eight others, the correlation was small but positive. The 24-h pattern in BP and wrist activity in controls was comparably phased; however, this was not the case for the transplant patients, indicating the day-night pattern in blood pressure in this group is strongly dependent on pathologic phenomena rather than activity level and pattern.     

飞秒激光辅助全板层角膜移植术治疗圆锥角膜临床观察

目的:评价飞秒激光辅助全板层角膜移植治疗圆锥角膜患者早期临床效果。方法:回顾性分析。15例17眼圆锥角膜患者均采用飞秒激光辅助联合Anwar大气泡技术暴露后弹力层的角膜移植手术。术前17只眼均测量裸眼视力(Uncorrected visual acuity,UCVA)、最佳矫正视力(Best corrected visual acuity,BCVA)、角膜内皮细胞计数(endothelial cell density,ECD)、角膜中央平均厚度、角膜曲率1(K1)、角膜曲率2(K2)、角膜地形图角膜散光度数和眼压(intraocular pressure,IOP)。所有患者随访时间为术后第1周、第1月、第2月和第3月。结果:到第3月时,UCVA和BCVA均有明显提高。测量中央角膜中央厚度为(493.0±46.80)μm;角膜曲率已接近正常水平,K1和K2平均值分别为(44.56±4.86)D和(40.22±3.60)D,以上数据与术前相比,差异均具有统计学意义(P0.001)。散光值下降至(4.57±3.60)D(P=0.185,P0.05)。角膜内皮细胞丢失率为14.3%。术后眼压均正常。结论:飞秒激光辅助全板层角膜移植治疗圆锥角膜患者早期临床效果明显,具有精确性、安全性和可预测性。     

Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells

Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival.     

Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol

Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration.Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication.     

Effects of anti‐human T lymphocyte immune globulins in patients: new or old

Multiple studies demonstrated that anti‐human T lymphocyte immune globulins (ATG) can decrease the incidence of acute and chronic graft rejection in cell or organ transplants. However, further in‐depth study indicates that different subgroups may benefit from either different regimes or alteration of them. Studies among renal transplant patients indicate that low immunological risk patients may not gain the same amount of benefit and thus tilt the risk versus benefit consideration. This may hold true for low immunological risk patients receiving other organ transplants and would be worth further investigation. The recovery time of T cells and natural killer (NK) cells also bears consideration and the impact that it has on the severity and incidence of opportunistic infections closely correlated with the dosage of ATG. The use of lower doses of ATG in combination with other induction medications may offer a solution. The finding that ATG may lose efficacy in cases of multiple transplants or re‐transplants in the case of heart transplants may hold true for other transplantations. This may lead to reconsideration of which induction therapies would be most beneficial in the clinical setting. These studies on ATG done on different patient groups will naturally not be applicable to all, but the evidence accrued from them as a whole may offer us new and different perspectives on how to approach and potentially solve the clinical question of how to best reduce the mortality associated with chronic host‐versus‐graft disease.     

血小板衍生生长因子对面部凹陷自体脂肪移植成活率的影响

目的:探讨血小板衍生生长因子(PDGF)对面部凹陷自体脂肪移植成活率的影响。方法:选取我院自2016年3月-2017年11月收治的62例面部凹陷患者,根据治疗方案的不同分为观察组和对照组,对照组30例患者仅采用自体脂肪颗粒移植治疗,观察组32例患者在对照组基础上加用血小板衍生生长因子治疗,比较两组患者治疗的优良率和并发症的发生情况。结果:治疗后,观察组患者的优良率为93.75%,明显高于对照组(73.33%,P0.05)。观察组患者治疗后3个月、6个月时身体脂肪吸收率明显高于术后1个月时(P0.05),且与对照组同时点比较,观察组患者治疗后3个月、6个月时的身体脂肪吸收率显著升高(P0.05)。观察组患者对治疗满意度为87.55%,显著高于对照组(70.0%,P0.05)。结论:血小板衍生生长因子应用于治疗面部凹陷能够有效提高自体脂肪移植的成活率。     

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

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Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool

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